Drug-free tumor therapy via spermine-responsive intracellular biomineralization

Chemotherapy based on molecular drugs remains the most frequently used approach for the therapy of tumors, however their poor specificity, severe side effects and tumor resistance often seriously hinder their applications. It is therefore desirable to develop a new, alternative therapeutic strategy for tumor treatment without traditional chemotherapeutic drugs. Herein, we report a drug-free tumor therapy approach involving spermine (SPM)-responsive intracellular biomineralization in tumor cells. In this work, we designed calcium carbonate (CaCO₃) nanoparticles capped with folic acid and supramolecular peptides, which could target tumor cells and rapidly self-aggregate into micron-sized CaCO₃ aggregates in SPM-overexpressed tumor cells. Due to the extended intracellular retention, CaCO₃ aggregates could induce intracellular biomineralization and Ca²⁺ overload of tumor cell, leading to mitochondrial damage and cellular apoptosis, resulting in effective inhibition of tumor growth without serious side effects otherwise seen in conventional chemotherapy.